United States Drug Patent 8,026,276: Scope, Claims, Expiration, and CCI-779 Patent Landscape

US Patent No. 8,026,276 covers injectable formulations of CCI-779, the active pharmaceutical ingredient later commercialized as temsirolimus in Torisel. Its core protection is directed to a two-part parenteral formulation: a CCI-779 concentrate containing ethanol, propylene glycol, vitamin E and, in several claims, citric acid; and a diluent containing polysorbate 80, polyethylene glycol 400 and ethanol.[1]

The patent is formulation-specific. It does not broadly cover temsirolimus as a chemical compound, all injectable temsirolimus products, or every solvent system. Its strongest claim coverage is concentrated around the disclosed solvent and surfactant system, component ratios, concentration ranges and preparation by combining the concentrate and diluent.

Public Orange Book records historically associated US 8,026,276 with Torisel. The patent term reached its ordinary statutory endpoint in 2023, subject to the precise terminal-disclaimer, patent-term-adjustment and pediatric-exclusivity records applicable to the patent and product.[2][3]

What does US Patent 8,026,276 protect?

US 8,026,276 protects parenteral compositions containing CCI-779 in a specific nonaqueous formulation platform. The principal components are:

Formulation element	Claimed material
Active ingredient	CCI-779, also known as temsirolimus
Primary solvent system	Dehydrated ethanol and propylene glycol
Antioxidant	d,l-alpha-tocopherol
Optional stabilizer	Citric acid
Diluent system	Polysorbate 80, polyethylene glycol 400 and dehydrated ethanol
Administration route	Parenteral
Product configuration	Concentrate plus diluent, or combined composition
Process protection	Combining the two mixtures, optionally with water

The claims use overlapping numerical ranges. The broadest concentration range for CCI-779 is approximately 1 to 25 mg/mL. Ethanol, propylene glycol, polysorbate 80 and polyethylene glycol 400 are generally claimed in ranges of about 15% to 60% w/v, although individual claims narrow those ranges.

The patent therefore protects a formulation architecture rather than a single commercial recipe.

How are the 24 claims organized?

The claims fall into five technical groups.

Claims 1 to 7: two-mixture formulations with citric acid

Claim 1 establishes the principal formulation combination:

A first mixture containing:
- 1 to 25 mg/mL CCI-779;
- 15% to 60% w/v dehydrated ethanol;
- 0.01% to 0.1% w/v d,l-alpha-tocopherol;
- 0.001% to 0.005% w/v citric acid; and
- 15% to 60% w/v propylene glycol.
A second mixture containing:
- 15% to 60% w/v polysorbate 80;
- 15% to 60% w/v polyethylene glycol 400; and
- 15% to 60% w/v dehydrated ethanol.

Claim 2 limits the first-to-second mixture ratio to approximately 1:1.5 to 1:2. Claims 3 and 4 narrow the composition to approximately 10 mg/mL CCI-779 and 0.0025% to 0.005% citric acid, respectively.

Claims 5 through 7 recite narrower formulations, including the following formulation values:

25 mg/mL CCI-779;
40% w/v ethanol in the first mixture;
0.075% w/v d,l-alpha-tocopherol;
0.0025% w/v citric acid;
35% w/v propylene glycol;
40% w/v polysorbate 80;
20% w/v polyethylene glycol 400; and
40% w/v ethanol in the second mixture.

Claim 7 uses “q.s.” for propylene glycol, meaning an amount sufficient to bring the formulation to the intended quantity. That language may create claim-construction issues because the claim does not provide a fixed final concentration for propylene glycol.

Claim 8: two-mixture formulation without citric acid

Claim 8 retains the ethanol, propylene glycol, tocopherol, polysorbate 80 and polyethylene glycol 400 system but omits citric acid from the first mixture.

This claim is potentially broader than claim 1 with respect to citric acid because a formulation may fall within claim 8 without including the claimed citric-acid range. It remains limited by the same general concentration ranges and parenteral-use requirement.

Claims 9 to 12: concentrate-and-diluent formulations

Claims 9 to 12 recast the two mixtures as a “concentrate” and a “diluent.”

Claim 9 requires the concentrate to contain:

1 to 25 mg/mL CCI-779;
0.01% to 0.1% d,l-alpha-tocopherol;
0.001% to 0.005% citric acid; and
15% to 60% w/v of dehydrated ethanol and propylene glycol.

The diluent contains:

15% to 60% w/v polysorbate 80;
15% to 60% w/v polyethylene glycol 400; and
15% to 60% w/v dehydrated ethanol.

Claims 10 and 11 narrow the concentrate-to-diluent ratio and CCI-779 concentration. Claim 12 removes citric acid from the concentrate.

The use of “consisting of” in claims 9 and 12 is significant. It can limit the claimed composition to the listed components, subject to the legal treatment of incidental impurities, residual processing materials and claim-construction principles.

Claims 13 to 19: ratio-based formulation claims

Claims 13 through 19 claim the ingredients as combined component groups rather than expressly as separate mixtures.

The key limitations are:

CCI-779: approximately 1 to 25 mg/mL;
d,l-alpha-tocopherol: 0.01% to 0.1% w/v;
citric acid, where required: 0.001% to 0.005% w/v;
ethanol plus propylene glycol: 15% to 60% w/v;
polysorbate 80 plus polyethylene glycol 400: 15% to 60% w/v;
polysorbate 80 to polyethylene glycol 400: approximately 1:1;
ethanol to propylene glycol: approximately 1.4:1;
each solvent mixture to CCI-779: approximately 50:1.

Claim 18 combines all these restrictions and is one of the narrowest claims in the patent. Claim 19 removes citric acid but retains the two 50:1 ratios and the 1.4:1 and 1:1 component ratios.

These claims create a quantitative infringement screen. A competing product that uses materially different solvent ratios, a different surfactant, a different polyethylene glycol grade or substantially different active-to-excipient ratios may avoid literal infringement, even if it is pharmaceutically similar.

Claims 20 to 22: fixed formulations

Claims 20 and 22 recite specific formulations rather than broad ranges.

Claim 20 includes approximately:

2.5% w/v CCI-779;
0.075% w/v d,l-alpha-tocopherol;
0.0025% w/v citric acid;
40% w/v dehydrated ethanol;
50% w/v propylene glycol;
40% w/v polysorbate 80;
20% w/v dehydrated ethanol; and
43% w/v polyethylene glycol 400.

Claim 22 recites:

1% w/v CCI-779;
0.03% w/v d,l-alpha-tocopherol;
0.001% w/v citric acid;
28% w/v ethanol;
20% w/v propylene glycol;
24% w/v polysorbate 80; and
26% w/v polyethylene glycol 400.

Claims 20 and 22 may provide narrower fallback positions if the broader range claims are vulnerable to prior-art or enablement challenges.

Claims 23 and 24: preparation process

Claim 23 covers combining the first and second mixtures. Claim 24 adds combining the mixtures with water.

These process claims are narrower than a general manufacturing claim. They require the claimed ingredients and the claimed combination step. They may be relevant to manufacturing operations even where the final product is not sold in the same two-vial or two-phase configuration.

Which claim limitations are most important for infringement?

The most important limitations are the formulation identity and quantitative relationships.

Limitation	Commercial significance
CCI-779 or temsirolimus	Identifies the active pharmaceutical ingredient
Parenteral composition	Excludes oral and nonparenteral products
Ethanol and propylene glycol	Defines the primary solvent platform
d,l-alpha-tocopherol	Narrows the antioxidant system
Citric acid	Applies to claims requiring the stabilizer
Polysorbate 80 and PEG 400	Defines the diluent and surfactant system
1:1 polysorbate 80/PEG 400 ratio	Narrows claims 14, 18 and 19
1.4:1 ethanol/propylene glycol ratio	Narrows claims 15, 18 and 19
Approximately 50:1 excipient-to-active ratios	Creates additional quantitative limitations
Concentrate-to-diluent ratio of 1:1.5 to 1:2	Applies to claims 2, 6, 10 and 21
Combining step	Required by process claims 23 and 24

The patent does not appear to require a particular vial, syringe, infusion bag, administration device or dosing schedule. A product could therefore fall within the composition claims without reproducing the same commercial packaging, provided the formulation meets the chemical and quantitative limitations.

What is the patent scope of “about” in these claims?

The repeated use of “about” expands the numerical boundaries beyond exact values, but it does not eliminate the need for a meaningful relationship to the stated range.

For example, a product containing 40% ethanol may be evaluated against a claim reciting “about 40%,” while a product containing a substantially different ethanol concentration may fall outside the limitation. The scope depends on the intrinsic evidence, prosecution history, specification, technical precision of the formulation and whether the difference affects formulation performance.

The ranges also overlap heavily. A formulation containing 10 mg/mL CCI-779, 40% ethanol, 35% propylene glycol, 0.075% tocopherol and 0.0025% citric acid would likely satisfy multiple independent and dependent claim pathways if the diluent and mixture ratios also align.

What patent protected the CCI-779 active ingredient?

US 8,026,276 is not the principal compound patent for CCI-779. CCI-779 is a rapamycin derivative, and earlier patents in the rapamycin-derivative field addressed the active ingredient and its therapeutic use.[4][5]

The relevant patent layers are:

Patent layer	Subject matter	Relevance
Rapamycin and derivative patents	Chemical structures and derivative compounds	Historical compound protection
Therapeutic-use patents	Treatment of cancer and other diseases with CCI-779 or rapamycin derivatives	Method-of-use exposure
Formulation patents	Injectable solvents, stabilizers, surfactants and concentrate/diluent systems	Direct relevance of US 8,026,276
Manufacturing patents	Preparation, purification or crystallization of temsirolimus	Potential supply-chain barriers
Regulatory exclusivity	FDA approval-based exclusivity	Separate from patent term

The earlier active-ingredient and use patents are distinct from the formulation claims in US 8,026,276. Expiration of the formulation patent does not itself establish that all historical CCI-779 patents expired on the same date.

What was the Orange Book status of US 8,026,276?

US 8,026,276 was associated with Torisel, the temsirolimus injection product approved by FDA under NDA 022088.[2][6]

The Orange Book identifies patents listed by the NDA holder and does not determine ultimate validity or infringement. A listed patent can be challenged through an Abbreviated New Drug Application Paragraph IV certification. Conversely, omission from the Orange Book does not necessarily eliminate exposure under non-Orange-Book patents, including manufacturing or method-of-use patents.

For US 8,026,276, the practical regulatory significance was its formulation relationship to Torisel. The patent’s ordinary statutory term ended in 2023 based on the applicable US filing and priority framework. Any pediatric extension or patent-term adjustment should be evaluated against the official Orange Book and USPTO term records rather than inferred from the issue date.[2][3]

When did temsirolimus lose exclusivity?

Temsirolimus lost the practical protection provided by US 8,026,276 when the patent term ended in 2023. FDA regulatory exclusivity and patent exclusivity are separate.

Torisel received FDA approval in 2007. FDA approval did not create a permanent barrier to generic entry. For a small-molecule injectable product, an ANDA applicant may challenge listed patents through Paragraph IV certification, certify that patents have expired, or seek approval after the listed patent term.

There is no biosimilar pathway for temsirolimus. Temsirolimus is a chemically synthesized small molecule, not a biologic. Competitors would generally use the ANDA pathway if an appropriate reference-listed drug and injectable product requirements are satisfied.[2][6]

Which companies challenged the Torisel patent estate?

Public records should be reviewed by ANDA number, applicant, FDA filing date and corresponding district-court docket before attributing a specific Paragraph IV challenge. The supplied claims alone do not establish the identity of any challenger, the filing date of a Paragraph IV certification, or the terms of any settlement agreement.

The commercial challenger universe would include generic injectable manufacturers with capabilities for:

sterile parenteral manufacturing;
handling ethanol and propylene glycol systems;
compatibility testing with polysorbate 80 and PEG 400;
container-closure qualification;
extractables and leachables testing; and
stability testing for a highly hydrophobic mTOR inhibitor.

A Paragraph IV challenge to US 8,026,276 would likely focus on claim construction, obviousness of the solvent and surfactant combination, written description, enablement, anticipation and the scope of “about.” A design-around could target the solvent ratio, omit citric acid where possible, alter the surfactant system, or use a different concentrate and diluent architecture.

How strong was the patent estate?

The patent had meaningful historical value because it targeted a difficult injectable formulation problem. CCI-779 is poorly water-soluble, and the claimed formulation uses a coordinated solvent, antioxidant, stabilizer and surfactant system.

Its strength varied by claim type:

Claim group	Relative breadth	Principal vulnerability
Claims 1 and 8	Moderate	Overlapping prior-art formulation systems and “about” construction
Claims 9 and 12	Moderate	Meaning of concentrate, diluent and “consisting of”
Claims 13 and 19	Narrow to moderate	Precise ratio limitations
Claims 18 and 20	Narrow	Design-around and nonliteral formulation differences
Claims 23 and 24	Narrow	Proof of the specific manufacturing sequence

The patent was stronger against a product that copied the Torisel formulation closely than against an alternative temsirolimus injectable using a materially different excipient system.

What manufacturing and formulation barriers remain after patent expiration?

Patent expiration does not remove technical barriers. A generic or follow-on manufacturer still must address:

sterility assurance;
particulate control;
solvent compatibility;
precipitation after dilution;
adsorption to container surfaces;
oxidation of excipients and active ingredient;
infusion-line compatibility;
stability after reconstitution or dilution;
preservative and antimicrobial strategy, if applicable;
container-closure integrity; and
bioequivalence for the injectable dosage form.

These issues can delay competition even after formulation patent expiration. They are regulatory and technical barriers, not continuing exclusivity rights under US 8,026,276.

How does US 8,026,276 compare with a conventional temsirolimus product claim?

A broad product claim might cover temsirolimus as an active ingredient in any pharmaceutical composition. US 8,026,276 is narrower because it requires a defined excipient environment.

Issue	Broad active-ingredient claim	US 8,026,276
Active ingredient	Temsirolimus or related compound	CCI-779
Dosage form	May be broad	Parenteral
Excipients	May be unrestricted	Defined ethanol, propylene glycol, tocopherol, citric acid and diluent components
Ratios	Usually absent	Central to several claims
Manufacturing step	Usually absent	Claims 23 and 24 require combining mixtures
Design-around potential	Low if compound claim remains active	Higher through formulation redesign

Key Takeaways

US 8,026,276 is a formulation patent for parenteral CCI-779, or temsirolimus.
Its core technology is a concentrate-and-diluent system using ethanol, propylene glycol, d,l-alpha-tocopherol, citric acid, polysorbate 80 and PEG 400.
Claims 1, 8, 9, 12 and 13 provide the principal composition coverage.
Claims 14 through 19 add precise excipient and active-ingredient ratios.
Claims 23 and 24 cover combining the formulation components, with claim 24 adding water.
The patent does not broadly claim temsirolimus as a compound or every injectable temsirolimus formulation.
US 8,026,276 was historically relevant to Torisel and its Orange Book patent estate.
The patent’s ordinary statutory term ended in 2023.
Temsirolimus is a small molecule, so biosimilar analysis does not apply.
Post-expiration competition remains subject to FDA injectable-product requirements and manufacturing complexity.
The principal design-around opportunities are changes to the solvent system, surfactant system, excipient ratios, citric-acid content and concentrate/diluent configuration.

FAQs About US Patent 8,026,276

Does US 8,026,276 cover Torisel itself?

It covers formulation embodiments associated with Torisel, not every possible temsirolimus product. A competing product must be compared against each asserted claim limitation.

Can a temsirolimus product avoid the patent by eliminating citric acid?

Potentially. Claims requiring citric acid may not read on a product without it. Claims 8 and 12 omit citric acid, so elimination alone would not avoid every claim.

Does a different surfactant avoid US 8,026,276?

A materially different surfactant may avoid claims requiring polysorbate 80, but the analysis must account for claim scope, equivalents and other patents.

Is a temsirolimus generic a biosimilar?

No. Temsirolimus is a chemically synthesized small molecule. A competing injectable product would generally proceed through the ANDA framework rather than the biosimilar pathway.

Does expiration of US 8,026,276 eliminate all temsirolimus patent risk?

No. Other compound, method-of-use, manufacturing or formulation patents may have existed separately. Each patent must be reviewed for claim scope, legal status and geographic coverage.

References

United States Patent No. 8,026,276. (2011). Pharmaceutical formulations of CCI-779. U.S. Patent and Trademark Office.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA, Center for Drug Evaluation and Research.
U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term information. U.S. Department of Commerce.
United States Patent No. 5,362,718. (1994). Pharmaceutical derivatives of rapamycin. U.S. Patent and Trademark Office.
United States Patent No. 6,277,983. (2001). Rapamycin derivatives. U.S. Patent and Trademark Office.
U.S. Food and Drug Administration. (2007). Torisel (temsirolimus) injection prescribing information. Pfizer Laboratories.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Pf Prism Cv	TORISEL	temsirolimus	SOLUTION;INTRAVENOUS	022088-001	May 30, 2007	AP	RX	Yes	Yes	8,026,276*PED	⤷ Start Trial			Y		⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	040693	⤷ Start Trial
Argentina	090603	⤷ Start Trial
Austria	385795	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,026,276

Which drugs does patent 8,026,276 protect, and when does it expire?

Summary for Patent: 8,026,276